Although this invention is being disclosed in connection with cervical cancer, it is applicable to many other areas of medicine. Uterine cervical cancer is the second most common cancer in women worldwide, with nearly 500,000 new cases and over 270,000 deaths annually (LARC, “Globocan 2002 database, “International agency for research in cancer, 2002, incorporated herein by reference). Because invasive disease is preceded by pre-malignant Cervical Intraepithelial Neoplasia (CIN), if detected early and treated adequately, cervical cancer can be universally prevented (D. G. Ferris, J. T. Cox, D. M. O'Connor, V. C. Wright, and J. Foerster, Modern Colposcopy, Textbook and Atlas, pp. 1-699, American Society for Colposcopy and Cervical Pathology, 2004, incorporated herein by reference). The pre cancerous epithelium is usually categorized as CIN grades 1, 2, and 3 or histologically low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL), depending on the severity of the lesions.
After an abnormal pap smear, colposcopy is the primary diagnostic tool for identifying the most atypical sites of the cervix for a biopsy. Cervical precursor lesions (Cervical neoplasias) exhibit certain morphologic features (features of form and structure) that can be identified during a colposcopic examination (D. G. Ferris, J. T. Cox, D. M. O'Connor, V. C. Wright, and J. Foerster, Modern Colposcopy. Textbook and Atlas, pp. 1-699, American Society for Colposcopy and Cervical Pathology, 2004, incorporated herein by reference). In particular, Cervical Intraepithelial Neoplasia (CIN), the abnormal growth of potential precancerous cells in the cervix, exhibits certain morphologic features that can be identified during a colposcopic exam. These features include distinct epithelial (membrane) and vascular (blood vessel) abnormalities.
The colposcopic examination is performed with high magnification, a bright light source and acetic acid. Cervical patterns are interpreted by clinically standardized criteria. The colposcopic examination determines the location of the most severe dysplastic (potentially cancerous) region for biopsy purposes. Dysplasia is a pathology term that is used to refer to the abnormal maturation of cells within a tissue. Metaplasia is a pathology term that is used to refer to the abnormal replacement of cells of one type by cells of another.
A fundamental part of the colposcopic exam is the use of acetic acid (vinegar). Potential precancerous epithelial cells in the cervix, such as immature metaplastic and dysplastic cervical squamous (having an outer layer of scale-like cells) epithelia, turn white after the application of acetic acid during an examination, to create acetowhite regions. Virtually all cervical cancer lesions become a transient and opaque white color following the application of 5% acetic acid. The whitening process (acetowhitening) occurs visually over several minutes and subjectively discriminates between dysphasic and normal tissue. An acetowhite region is one of the major colposcopic signs observed in cervical cancer. The spatial location and temporal changes of acetowhite regions are the major visual diagnostic indicators in the exam, and are usually interpreted by a trained colposcopist based upon prior experience. However, blood vessels do not turn white after application of acetic acid and therefore still appear red, even though they are in abnormal tissue that has become white, so that blood vessels may mask acetowhitening.
Further, some lesions do not have visible blood vessels, and some normal regions are naturally white, or turn white after application of acetic acid, so reliance solely on acetowhitening leads to substantial amounts of false positive results.
Due to the subjective nature of a colposcopic examination, the accuracy of colposcopy is highly dependent upon colposcopists' experience and expertise. It has been estimated that approximately one third of high grade disease is missed by initial colposcopy, so that there are also substantial amounts of false negative results (T. Cox, M. Schiffnan, and D. Solomon, “Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy”, American Journal of Obstetrics and Gynecology, 188, pp. 1406-1412, 2003, incorporated herein by reference). The advent of digitized medical images has led to an increasingly important and evolving role for image processing and computer-aided diagnostic (CAD) systems. An automated image analysis system that identifies and analyzes diagnostic features in uterine cervical images is desirable, and could provide a clinical diagnosis by following an objective and quantifiable process, which together with the subjective judgment of a colposcopist, could increase accuracy and reduce false positives and false negatives.
Digital imaging technologies could assist physicians in analyzing the acetic acid induced lesions (acetowhite regions) in a fully automatic and objective way. However, automated detection of acetowhite epithelial depicted on cervical images has been a challenging task due to light reflection, varying amounts of illumination and wide inter- and intra-patient variation. There is also the problem of false positives, because, as noted above, human cervical tissue may naturally be white in some patients and thus may look like an acetowhite lesion. False positives are also derived from imperfect registration (alignment) of pre and post acetic acid images. It is a goal of the present invention to increase the accuracy of, and reduce the incidence of false positives (and false negatives) in, colposcopic examinations.
It is therefore an object of the present invention to provide computer aided cervical cancer diagnosis using image processing algorithms for automatic objective diagnosis. It is another object of the present invention to find numeric measurements which can be quantitatively correlated to lesion stage, and thereby provide higher predictive value for the presence of cancer.
The following patents and patent applications may be considered relevant to the field of the invention:
U.S. Pat. No. 6,902,935 to Kaufman et al., incorporated herein by reference, provides methods and systems for monitoring effects of chemical agents on optical signals produced by a sample in response to chemical agents.
U.S. Pat. No. 7,260,248 to Kaufman et al, incorporated herein by reference, discloses methods of relating a plurality of images that are used in the segmentation of a sequence of colposcopic images. The methods are applied to determine tissue characteristics in acetowhitening testing of cervical cancer.
U.S. Pat. No. 7,309,867 to Costa et al., incorporated herein by reference, discloses methods for determining the probability that a given region of tissue sample contains tissue of a given category, such as cervical intraepithelial neoplasia, grades 1, 2, and/or 3.
U.S. Patent Application No. 2006/0228015 to Brockway et al., incorporated herein by reference, discloses a method for processing an image of a region of interest to detect abnormalities such as lesions by analyzing spatial information, feature templates, morphology parameters, and intensity parameters that vary over time.